scholarly journals Effect of Prophylactic Vaccination with the Membrane-Bound Acid Phosphatase Gene of Leishmania mexicana in the Murine Model of Localized Cutaneous Leishmaniasis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
María Angélica Burgos-Reyes ◽  
Lidia Baylón-Pacheco ◽  
Patricia Espíritu-Gordillo ◽  
Silvia Galindo-Gómez ◽  
Víctor Tsutsumi ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Murine Model ◽  
Clinical Manifestations ◽  
Protozoan Parasite ◽  
Effective Vaccine ◽  
Preventive Strategy ◽  
Leishmania Mexicana ◽  
T Helper 1 ◽  
Lymphoproliferative Response ◽  
Prophylactic Vaccination

Leishmaniasis is a disease caused by an intracellular protozoan parasite of the genus Leishmania. Current treatments for leishmaniasis are long, toxic, and expensive and are not available in some endemic regions. Attempts to develop an effective vaccine are feasible, but no vaccine is in active clinical use. In this study, the LmxMBA gene of Leishmania mexicana was selected as a possible vaccine candidate using the reverse vaccinology approach, and the prophylactic effect generated by DNA vaccination with this gene in a murine model of cutaneous leishmaniasis was evaluated. The results showed that prophylactic vaccination with pVAX1::LmxMBA significantly reduced the size of the lesion and the parasitic load on the footpad, compared to the control groups. At a histological level, a smaller number of parasites were evident in the dermis, as well as the absence of connective tissue damage. Mice immunized with plasmid pVAX1::LmxMBA induced immunity characterized by an increase in the IgG 2 a / IgG 1 > 1 ratio and a higher rate of lymphocyte proliferation. In this study, immunization with the plasmid promoted an improvement in the macroscopic and microscopic clinical manifestations of the experimental infection by L. mexicana, with a T helper 1 response characterized by an IgG 2 a / IgG 1 > 1 ratio and high lymphoproliferative response. These findings support immunization with the plasmid pVAX1::LmxMBA as a preventive strategy against cutaneous infection of L. mexicana.

scholarly journals Differential Regulation of L-Arginine Metabolism through Arginase 1 during Infection with Leishmania mexicana Isolates Obtained from Patients with Localized and Diffuse Cutaneous Leishmaniasis

2020 ◽  
Vol 88 (7) ◽  
Author(s):  
Arturo A. Wilkins-Rodríguez ◽  
Armando Pérez-Torres ◽  
Alma R. Escalona-Montaño ◽  
Laila Gutiérrez-Kobeh
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Clinical Manifestations ◽  
Differential Regulation ◽  
Leishmania Mexicana ◽  
Arginine Metabolism ◽  
Content Type ◽  
Arginase 1 ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

ABSTRACT l-Arginine metabolism through arginase 1 (Arg-1) and inducible nitric oxide synthase (NOS2) constitutes a fundamental axis for the resolution or progression of leishmaniasis. Infection with Leishmania mexicana can cause two distinct clinical manifestations: localized cutaneous leishmaniasis (LCL) and diffuse cutaneous leishmaniasis (DCL). In this work, we analyzed in an in vivo model the capacity of two L. mexicana isolates, one obtained from a patient with LCL and the other from a patient with DCL, to regulate the metabolism of l-arginine through Arg-1 and NOS2. Susceptible BALB/c mice were infected with L. mexicana isolates from both clinical manifestations, and the evolution of the infection as well as protein presence and activity of Arg-1 and NOS2 were evaluated. The lesions of mice infected with the DCL isolate were bigger, had higher parasite loads, and showed greater protein presence and enzymatic activity of Arg-1 than the lesions of mice infected with the LCL isolate. In contrast, NOS2 protein synthesis was poorly or not induced in the lesions of mice infected with the LCL or DCL isolate. The immunochemistry analysis of the lesions allowed the identification of highly parasitized macrophages positive for Arg-1, while no staining for NOS2 was found. In addition, we observed in lesions of patients with DCL macrophages with higher parasite loads and stronger Arg-1 staining than those in lesions of patients with LCL. Our results suggest that L. mexicana isolates obtained from patients with LCL or DCL exhibit different virulence or pathogenicity degrees and differentially regulate l-arginine metabolism through Arg-1.

scholarly journals Evaluation of the lymphoproliferation of mononuclear cells in cutaneous leishmaniasis patients treated with Libidibia ferrea

2021 ◽  
Vol 5 (3) ◽  
pp. 97
Author(s):  
Erika Oliveira Da Silva ◽  
Paula Figliuolo da Cruz Borges ◽  
Rafaela Benício Santana ◽  
Heriederson Sávio Dias Moura ◽  
José Fernando Marques Barcellos ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Mononuclear Cells ◽  
Clinical Manifestations ◽  
Immunomodulatory Activity ◽  
Parasitic Diseases ◽  
Healthy Individuals ◽  
Lymphoproliferative Response ◽  
Peripheral Blood Mononuclear ◽  
Significant Difference ◽  
Before And After

American integumentary leishmaniasis (ATL) is a neglected disease that mostly affects vulnerable populations. Its broad spectrum of clinical manifestations is related to the type of immune response produced by the host and the species of Leishmania involved. In recent years, the use of medicinal plants has become a therapeutic alternative in the treatment of infectious parasitic diseases. This research aimed to evaluate the lymphoproliferative responses of peripheral blood mononuclear cells (PBMCs) of patients with cutaneous leishmaniasis (CL) before and after treatment, and healthy individuals. The lymphoproliferative response was evaluated in cell culture using stimuli of the dichloromethane fraction (DCM) obtained from Libidibia ferrea, Glucantime® and phytohemagglutinin - PHA using a BrdU Cell Proliferation after 72 h of incubation. In cultures treated with the DCM fraction, intense induction of lymphoproliferation was observed (p<0.0001), as was also observed in response to the PHA mitogen, and there was a significant difference when compared with the conventional treatment (p<0.0135). In the post-treatment and healthy groups, although the compound induced lymphoproliferation, there was no statistical difference. These results suggest that the organic compound played an important inducing role in lymphoproliferation, which highlights the importance of continuity involving new studies in order to evaluate its immunomodulatory activity.

scholarly journals 766. Everything Old is New Again-A Case Series of New World Leishmaniasis in African Children in Portland, Maine

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S428-S428
Author(s):  
Jennifer Jubulis ◽  
Amanda Goddard ◽  
Elizabeth Seiverling ◽  
Marc Kimball ◽  
Carol A McCarthy
Keyword(s):  
Latin America ◽  
Cutaneous Leishmaniasis ◽  
New World ◽  
Pediatric Patients ◽  
Data Extraction ◽  
Clinical Manifestations ◽  
Case Series ◽  
Surgical Excision ◽  
Skin Lesions ◽  
Travel History

Abstract Background Leishmaniasis has many clinical manifestations and treatment regimens, dependent on species and host. Old world leishmaniasis is found primarily in Africa and Asia, and is associated with visceral disease, while new world disease, seen primarily in Latin America, is more commonly mucocutaneous. We present a case series of pediatric African patients with New World cutaneous leishmaniasis (NWCL). Methods Data extraction was performed via chart review, analyzing travel history, clinical presentation, diagnosis, and management in children with cutaneous leishmaniasis presenting to the pediatric infectious diseases clinic in Portland, ME. Biopsy specimens were sent to the federal CDC for identification by PCR and culture. Results Five cases of NWCL were diagnosed in pediatric patients in Maine from November 2018 through February 2020. Median age of patients was 10 years (range 1.5-15 years). Four cases (80%) occurred in children from Angola or Democratic Republic of Congo, arriving in Maine via Central/South America, with one case in a child from Rwanda who arrived in Maine via Texas. Three patients had multiple skin lesions and two had isolated facial lesions. Leishmaniasis was not initially suspected resulting in median time to diagnosis of 5 months (range 1-7 months). Four patients were initially treated with antibacterials for cellulitis and one was treated with griseofulvin. After no improvement, patients underwent biopsy with 2 patients diagnosed with L panamensis, 1 with L braziliensis, 1 with mixed infection (L panamensis and L mexicana), and 1 with Leishmania species only. One patient was managed with surgical excision, 3 with ketoconazole, and 1 was observed off therapy. Four patients were referred to otolaryngology. All continue to be followed in infectious disease clinic. Conclusion We present five cases of new world cutaneous leishmaniasis in African pediatric patients arriving to Maine through Latin America or Texas. Patients were diagnosed with cellulitis, tinea corporis or atopic dermatitis initially, underscoring importance of high index of suspicion in migrant patients. Detailed travel history and epidemiologic knowledge is essential to diagnosis, as patients may present with illness not congruent with country of origin. Optimal therapy remains unclear. Disclosures All Authors: No reported disclosures

scholarly journals Effects of topical gel formulation of Ficus carica latex on cutaneous leishmaniasis induced by Leishmania major in BALB/c mice

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Ali Pouryousef ◽  
Erfan Eslami ◽  
Sepehr Shahriarirad ◽  
Sina Zoghi ◽  
Mehdi Emami ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Murine Model ◽  
Leishmania Major ◽  
Considerable Effect ◽  
Ficus Carica ◽  
Control Group ◽  
Topical Gel ◽  
The Third ◽  
Mean Size ◽  
The Mean

Abstract Objectives The current study aimed to evaluate the effects of Ficus carica latex on the treatment of cutaneous leishmaniasis (CL), induced by Leishmania major. A 5% topical gel with F. carica latex was prepared. BALB/c mice were infected by inoculation of amastigotes form of L. major. Thirty BALB/c mice were divided into five groups, where the first group was treated daily, the second group twice per day, and the third group every other day with the 5% topical gel, for 3 weeks. The sizes of the lesions were measured before and during the course of treatment. Results Although the mean size of lesions in the mice group treated with the 5% F. carica gel, especially in the group receiving daily treatment, was less than the mean size of the lesions in the control group, yet, the differences was not statistically significant (p > 0.05). The findings of the current study demonstrated that the 5% F. carica latex with a 3-week course of treatment had no considerable effect in recovery or control of CL induced by L. major in the murine model. Using higher concentration of F. carica latex and with longer treatment lengths may increase its efficacy in the treatment of CL.

scholarly journals Ruthenium-Clotrimazole complex has significant efficacy in the murine model of cutaneous leishmaniasis

Acta Tropica ◽  
2016 ◽  
Vol 164 ◽  
pp. 402-410 ◽  
Author(s):  
Eva Iniguez ◽  
Armando Varela-Ramirez ◽  
Alberto Martínez ◽  
Caresse L. Torres ◽  
Roberto A. Sánchez-Delgado ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Murine Model ◽  
Significant Efficacy

Influence of Obesity on Clinical Manifestations and Response to Therapy in Cutaneous Leishmaniasis caused by Leishmania braziliensis

2021 ◽  
Author(s):  
Tainã Lago ◽  
Lucas Carvalho ◽  
Mauricio Nascimento ◽  
Luiz H Guimarães ◽  
Jamile Lago ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Clinical Presentation ◽  
Clinical Manifestations ◽  
Healing Time ◽  
Response To Therapy ◽  
Leishmania Braziliensis ◽  
Cutaneous Lesions ◽  
Cytokine Levels ◽  
Cure Rates ◽  
The Impact

Abstract Background Cutaneous leishmaniasis (CL) caused by L. braziliensis is characterized by a single ulcer or multiple cutaneous lesions with raised borders. Cure rates below 60% are observed in response to meglumine antimoniate therapy. We investigated the impact of obesity on CL clinical presentation and therapeutic response. Methods A total of 90 age-matched CL patients were included (30 obese, 30 overweight and 30 with normal BMI). CL was diagnosed through documentation of L. braziliensis DNA by PCR or identification of amastigotes in biopsied skin lesion samples. Serum cytokine levels were determined by chemiluminescence. Antimony therapy with Glucantime (20mg/kg/day) was administered for 20 days. Results Obese CL patients may present hypertrophic ulcers rather than typical oval, ulcerated lesions. A direct correlation between BMI and healing time was noted. After one course of Antimony, cure was achieved in 73% of patients with normal BMI, 37% of overweight subjects, yet just 18% of obese CL patients (p&lt;0.01). Obese CL cases additionally presented higher leptin levels than overweight patients or those with normal BMI (p&lt;0.05). Conclusions Obesity modifies the clinical presentation of CL and host immune response, and is associated with greater failure to therapy.

scholarly journals Viremia in Equine Herpes Virus-1 infection and a possible link to Transient Protective Immunity

2021 ◽  
Vol 9 (1) ◽  
pp. 11-16
Author(s):  
AR Awan ◽  
OL Tulp ◽  
HJ Field
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Murine Model ◽  
Herpes Virus ◽  
Natural Infection ◽  
Fluorescent Antibody ◽  
Buffy Coat ◽  
Effective Vaccine ◽  
Infection Model ◽  
Herpès Virus

Equine herpes virus (EHV-1) causes respiratory infections in equine, and results in abortion, paresis, neonatal death, and retinopathy and the virus may become latent following initial infection. Virus entry is via the respiratory route, and the virus replicates in the host in ciliated and non-ciliated epithelial cells of the respiratory tract and in Type 1 and Type 2 pneumocytes in the lung parenchyma. After viral replication in the respiratory system, the virus can become disseminated to other parts of body via viraemic cells. The virus also can cross the placenta which leads to abortion of live or dead fetuses without premonitory signs. Infected horses show transient immunity after natural or experimental infection and immune responses to EHV-1, but the immunoprotective status begins to decline after a few months of active infection. Due to the transient immune response, recovered horses are not immunoprotected and thus are prone to subsequent re-infection. Immunity is not long lived after experimental or natural infection, and as a result the development of an effective vaccine has remained a challenge. In this study viraemic cells were studied in a murine EHV-1 infection model. Mice were infected intranasally and viraemic cells were studied on days three and five which occurs during the peak of the infection. The results of this study may help to identify the nature of viraemic cells and their role in the transient immune response to infection. Buffy coat cells and lungs were removed and stained with a fluorescent antibody test for EHV-1 antigen, and lung specimens were subjected to transmission electron microscopy. Both techniques confirmed the presence of viraemic cells in lung tissues. These viraemic cells were further stained for EHV-1 antigen, and for CD4 or CD8 biomarkers and results are discussed re: pathogenesis of EHV-1 infection, identification of viraemic cells in a murine model and possible link of viraemia to transient immune responses in EHV-1 infection, which demonstrate the validity of this murine model for the investigation of the cytopathologic mechanism and sequelae of EHV manifestation in this model.

scholarly journals A Novel Bacterium-Like Particle-Based Vaccine Displaying the SUDV Glycoprotein Induces Potent Humoral and Cellular Immune Responses in Mice

Viruses ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1149
Author(s):  
Shengnan Xu ◽  
Cuicui Jiao ◽  
Hongli Jin ◽  
Wujian Li ◽  
Entao Li ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Surface Display ◽  
Neutralizing Antibody ◽  
Hemorrhagic Fever ◽  
Poly I:C ◽  
Cell Mediated Immunity ◽  
T Helper ◽  
T Helper 1 ◽  
Prophylactic Vaccination ◽  
Cellular Immune

Sudan virus (SUDV) causes severe lethal hemorrhagic fever in humans and nonhuman primates. The most effective and economical way to protect against Sudan ebolavirus disease is prophylactic vaccination. However, there are no licensed vaccines to prevent SUDV infections. In this study, a bacterium-like particle (BLP)-based vaccine displaying the extracellular domain of the SUDV glycoprotein (eGP) was developed based on a gram-positive enhancer matrix-protein anchor (GEM-PA) surface display system. Expression of the recombinant GEM-displayed eGP (eGP-PA-GEM) was verified by Western blotting and immunofluorescence assays. The SUDV BLPs (SBLPs), which were mixed with Montanide ISA 201VG plus Poly (I:C) combined adjuvant, could induce high SUDV GP-specific IgG titers of up to 1:40,960 and robust virus-neutralizing antibody titers reached 1:460. The SBLP also elicited T-helper 1 (Th1) and T-helper 2 (Th2) cell-mediated immunity. These data indicate that the SBLP subunit vaccine has the potential to be developed into a promising candidate vaccine against SUDV infections.

scholarly journals Suicidal Leishmania

Pathogens ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 79 ◽  
Author(s):  
Lucie Podešvová ◽  
Tereza Leštinová ◽  
Eva Horáková ◽  
Julius Lukeš ◽  
Petr Volf ◽  
...  
Keyword(s):  
Cell Death ◽  
Phospholipase A2 ◽  
Cutaneous Leishmaniasis ◽  
Human Pathogen ◽  
Leishmania Mexicana ◽  
Macrophage Infection ◽  
Obligate Intracellular ◽  
Intracellular Parasites ◽  
Tropical Infections

Leishmania are obligate intracellular parasites known to have developed successful ways of efficient immunity evasion. Because of this, leishmaniasis, a disease caused by these flagellated protists, is ranked as one of the most serious tropical infections worldwide. Neither prophylactic medication, nor vaccination has been developed thus far, even though the infection has usually led to strong and long-lasting immunity. In this paper, we describe a “suicidal” system established in Leishmania mexicana, a human pathogen causing cutaneous leishmaniasis. This system is based on the expression and (de)stabilization of a basic phospholipase A2 toxin from the Bothrops pauloensis snake venom, which leads to the inducible cell death of the parasites in vitro. Furthermore, the suicidal strain was highly attenuated during macrophage infection, regardless of the toxin stabilization. Such a deliberately weakened parasite could be used to vaccinate the host, as its viability is regulated by the toxin stabilization, causing a profoundly reduced pathogenesis.

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